A novel platform for arming of candidate oncolytic viruses targeting immunologically cold metastatic ovarian cancer

Ovarian cancer (OC) is the 6th most common cause of cancer death. Annually \≫7,443 women are diagnosed (\≫240,000 globally). Mortality rates are \≫65%, with most patients succumbing within 5-years.

OC is frequently diagnosed at a late stage making it difficult to treat. Whilst initial response to chemotherapy is high, most patients (\≫80%) quickly acquire (platinum-)resistance and relapse. Second-line chemotherapies/targeted-biologicals offer only marginal benefit in slowing progression.

Emerging immunotherapies empower the patient's immune system to fight cancer and offer hope as effective second-line treatments. However, most (\≫85%) OC tumours are devoid of essential immune cells/processes, making them unresponsive to immunotherapies.

Oncolytic viruses (OVs) act by selectively infecting/destroying cancer cells, whilst simultaneously stimulating strong immune responses (recruiting immune cells/lifting cancer-associated immune suppression). A key strength of OVs is the ability to arm them with one/more synergistic therapeutic transgenes that may be expressed directly within the tumour (enhancing efficacy/bypassing toxicities).

However, existing OVs are derived from re-purposed/common laboratory/wild-type viruses that are not evolved for oncolytic use nor systemic delivery, but instead developed/validated using laboratory cell-lines or mice that poorly reflect patient tumours. Typical arming strategies select 1-2 transgenes (from thousands of options) using a 'best-guess' approach on basic models (often de-selecting candidates with efficacy in real tumours, and poorly synergising with the virus). They give little attention to optimising transgene position within the virus (a critical variable for effective transgene expression).

Theolytics seek to overcome these challenges through application of their disruptive OV Platform.